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Metabolic Acidosis Alex Flaxman, MD, MSE Presentation 50 yo M, 4d h/o vomiting & R inf chest/RUQ pn Wife adds 10-15 lb wt loss x4d and lethargic, sleeping “23 hrs/day” Vomiting: – After eating, but also when doesn’t eat, NBNB. Has been able to tolerate Gatorade, and has increased his intake of Gatorade. Pain: – R-sided, underneath ribs, occ rad to L “Prior’s” Pt in ED MICU 8/04 for same – S/p CTAP, UGI & LGI endoscopy – Investigated for toxidrome – Denies EtOH, home-made alcohol, antifreeze, ethylene glycol, MeOH, pica, or other tox exposures. DOH visit to home. EGD 6 wks ago for N/V, neg as per pt Travel 3 wks ago to Palm Beach, FL ROS General: CV: Resp: GI: GU: -chills, +fatigue CP SOB, Cough N/V, abd pn, -diarrhea, -blood -freq/hematuria/urgency All: PMH: PSH: Meds: PMD: NKDA Depression x2yrs, hyperchol, disc herniations L3, L4, L5 s/p bk inj Laminectomy x2, UGI, LGI, EGD 6 wks ago Compazine x1d, Nexium, Zoloft, Vicodin, Somma @BI Tobacco: EtOH: Drugs: 1 ppd, h/o 2-3 ppd Denies Denies Vital Signs BP P R O2 T Pn 161/103 129 24 97% 99.4 PR 10/10 Exam General: Pul: CV: Abd: Rectal: Ext: WDWN, NAD, tachypneic CTAB Tachy, reg, S1, S2, -m/r/g NABS, RUQ tend, epig tend, +massesliver edge ~ 9 cm inf to costal margin Guaiac neg w/ no stool -edema, hyperpig L foot cool R PT 2+ DP +Doppler L PT +Doppler DP +Doppler EKG SR @ 124 w/ LAE ? Q II, aVF (new from 8/31/04) ? ST elev V2, V3 Sinus tach new from 8/21/04 CXR NAD, -free air NG Lavage Yellow-green material, no blood What labs do you want? Labs 136 112 3 179 4.3 6 1 17.1 16.3 50.9 10.3 13.6 1.2 31.5 Lipase 159 Troponin 0.02 465 N 96 L3 M3 More Labs AST ALT Alk TB DB Alb TP 74 6 163 3.6 0 5.2 9.7 UA Cloudy Prot 100 WBC 0-5 RBC 0-3 Hyaline Casts 0-5 Lactate 2.2 Acetone neg EtOH 0 Serum osmolarity 290 Now What? ABG 7.12 / 18 / 105 / RA / 8.3 Recall 136 112 6 Rule 1: Acidosis or Alkalosis 7.12 / 18 / 105 / RA / 8.3 Acidosis Rule 2: Metabolic, Respiratory, Both 7.12 / 18 / 105 / RA / 8.3 Metabolic Rule 3: Anion Gap AG = ? 7.12 / 18 / 105 / RA / 8.3 136 112 6 = Na – Cl – HCO3 = 136 – 112 – 6 = 18 So we have an… Anion Gap Metabolic Acidosis Rule 4: Degree of Compensation For metabolic acidosis, Expected PCO = 1.5(HCO3) + 8 ± 2 2 = 1.5(6) + 8 ± 2 =9+8±2 = 17 ± 2 = 15, 19 7.12 / 18 / 105 / RA / 8.3 Actual PCO is 18 appropriate compensation 2 Rule #5: δ/δ 7.12 / 18 / 105 / RA / 8.3 136 112 6 AG Any takers? = 18 (nl 6.6-10.6) HCO3 = 6 (nl 24) Rule #5: δ/δ AG should be 10 but is now 18, for a difference of 8 The AG went up by 8, so the HCO3 should go down by 8. So HCO3 should be 24 – 8 = 16 but is really 6. The HCO3 is lower than predicted so there is also a concurrent non-AG metabolic acidosis. Causes of AG Metabolic Acidosis MUD PILES Methanol: wood alcohol, grain alcohol (moonshine), paint thinners, windshield washer fluid Uremia DKA, AKA Paraldehyde, propylene glycol Ingestions (INH, iron, XTC, cocaine) Lactic Acidosis EtOH, Ethylene glycol Salicylates Other causes “P” – Phenformin Toluene poisoning (glue sniffing) Other organic acids – Lactic acid – Acetone – Ketoacids: hydroxybutyrate / acetoacetate – Hippuric Acid – 5-oxyproline – Salicylates Lactic Acidosis Usually increase in the L isomer – Type A 2° to hypoxia (hypoperfusion, sepsis) – Type B Not d.t. hypoxia: seizures, liver failure, thiamine deficiency D-Lactic Acidosis- increase in the D isomer D-Lactate D-Lactate: External Sources Ingestion of fermented fruits and vegetables: pickles, yogurt, sauerkraut LR and dialysate contain dl-lactate (50/50) Propylene glycol ?metabolism? D-Lactate: Internal Sources In the gut, glucose is metabolized by flora to lactate: l-Lactate d-Lactate Produced via the methyl-glyoxal pathway (part of threonine catabolism) (threonine is an essential amino acid) D-Lactate: Internal Sources Pyruvate ↔ dl-Lactate via Lactate Dehydrogenase BUT Pyruvate ↔ l-Lactate requires l-LDH Pyruvate ↔ d-Lactate requires d-LDH Mammals do not have d-LDH D-Lactate: Getting rid of it Slowly metabolized? Not. d-hydroxy-acid-dehydrogenase – Mitochondrial enzyme – In many tissues (especially liver and kidney) – Converts d-lactate (and other substrates) to pyruvate But overall, d-lactate is metabolized more slowly than l-lactate D-Lactic Acidosis An increase in D-Lactate (duh) Symptoms Tachypnea AMS Slurred speech Confusion Inability to concentrate Somnolence Hallucinations Clumsiness Weakness Ataxia / unsteady gait Nystagmus Irritable Abusive behavior Ptosis Asterixis Risk Factor Anything that results in increased delivery of undigested carbohydrates to the colon Risk Factors Short Bowel Syndrome #1 Surgical resection #2 Intestinal bypass (bariatric surgery) – Feeding tube placement Intestinal malabsorption? – Chronic pancreatitis Risk Factors Not from the H&P Alteration of normal colon flora to a predominance of Gm+ anaerobes (lactobacillus) ? Colonic stagnation Impaired metabolism Precipitating Factors Excessive oral food intake – Especially carbohydrates (like Gatorade) Change in enteral feeding formula Labs Renal function normal or abnormal AG Metabolic acidosis – Can have non-AG metabolic acidosis Elevated serum or urine D-lactate – Serum level > 3 mmol/L Ancillary Tests LP: CSF D-lactate levels same as serum EEG: b/l diffuse, high-voltage slow waves without focal abnormality Stool culture: predominance of Gm+ anaerobic organisms – Lactobacillus – Bifidobacterium – Eubacterium Immediate Treatment A-B-C NPO IV dextrose (e.g. D5NS) Treatment Supportive Adjust feeding tube Adjust enteral feeding formula Change diet to starch instead of carbohydrates recurrent attacks Surgical: reanastomosis Oral abx: neomycin, vanco, kanamycin, metro Bicarb- unclear Treatment Increase luminal pH – CaCO3, MgCl2 – HCO3 Abx – Oral vanco, metro, or neomycin Although can cause overgrowth of lactobacillus Dialysis – Corrects acidosis – Clears d-Lactate Other Interesting Points d-Lactate levels correlate poorly with symptoms Normal humans infused with d-lactate do not develop symptoms Other acidoses to the same pH do not cause similar symptoms Final dorky Interesting Point 7.12 / 18 / 105 / RA / 8.3 136 112 6 AG metabolic acidosis and concurrent non-AG metabolic acidosis Why? Final dorky Interesting Point In D-lactate acidosis the increase in the AG tends to be less than the decrease in the HCO3. In L-lactic acidosis where the increase in the AG tends to be greater than the reduction in the bicarb. Final dorky Interesting Point 1. Much lower renal threshold for d-lactate than for l-lactate 2. Loss of the sodium salt of D-lactic acid in the stool (the H+ is resorbed from the lumen or reacts with secreted HCO3) but the organic ion does not Take Home Points- General 1. Consider ABG’s more often 2. Look for causes of metabolic acidosis 3. In unclear cases, or cases where MUD PILES fails, send tests for organic acids (e.g. dlactate and ß-hydroxybutyrate) 4. Involve intensivist early Take Home Points- d-Lactate 1. For patients with short bowel (or other malabsorption risks), consider D-lactic acidosis. 2. Also consider when AG acidosis and: a) Nl “lactate” levels and no acetone b) Short bowel or other malabsorption syndrome c) Preceded by food ingestion (and symptoms improve after discontinuation) d) Characteristic neurological findings